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Myeloid derived suppressor cells

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https://www.readbyqxmd.com/read/29334374/transitory-presence-of-myeloid-derived-suppressor-cells-in-neonates-is-critical-for-control-of-inflammation
#1
Yu-Mei He, Xing Li, Michela Perego, Yulia Nefedova, Andrew V Kossenkov, Erik A Jensen, Valerian Kagan, Yu-Feng Liu, Shu-Yu Fu, Qing-Jian Ye, Yan-Hong Zhou, Lai Wei, Dmitry I Gabrilovich, Jie Zhou
Myeloid-derived suppressor cells (MDSCs) are pathologically activated and relatively immature myeloid cells that have been implicated in the immunological regulation of many pathologic conditions. Phenotypically and morphologically, MDSCs are similar to neutrophils (PMN-MDSCs) and monocytes (M-MDSCs). However, they have potent suppressive activity and distinct gene expression profiles and biochemical characteristics. No or very few MDSCs are observed in steady-state physiological conditions. Therefore, until recently, accumulation of MDSCs was considered a consequence of pathological processes or pregnancy...
January 15, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29331323/regulation-of-inflammatory-factors-by-double-stranded-rna-receptors-in-breast-cancer-cells
#2
Amritha Venkatesh, Harika Nandigam, Maria Muccioli, Manindra Singh, Tiffany Loftus, Deana Lewis, Michelle Pate, Fabian Benencia
Malignant cells are not the only components of a tumor mass since other cells (e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part of it. In combination with the extracellular matrix, all these cells constitute the tumor microenvironment. In the last decade the role of the tumor microenvironment in cancer progression has gained increased attention and prompted efforts directed to abrogate its deleterious effects on anti-cancer therapies. The immune system can detect and attack tumor cells, and tumor-infiltrating lymphocytes (particularly CD8 T cells) have been associated with improved survival or better response to therapies in colorectal, melanoma, breast, prostate and ovarian cancer patients among others...
November 22, 2017: Immunobiology
https://www.readbyqxmd.com/read/29322091/a-retroviral-replicating-vector-encoding-cytosine-deaminase-and-5-fc-induces-immune-memory-in-metastatic-colorectal-cancer-models
#3
Kader Yagiz, Maria E Rodriguez-Aguirre, Fernando Lopez Espinoza, Tiffany T Montellano, Daniel Mendoza, Leah A Mitchell, Carlos E Ibanez, Noriyuki Kasahara, Harry E Gruber, Douglas J Jolly, Joan M Robbins
Treatment of tumors with Toca 511, a gamma retroviral replicating vector encoding cytosine deaminase, followed by 5-fluorocytosine (5-FC) kills tumors by local production of 5-fluorouracil (5-FU). In brain tumor models, this treatment induces systemic anti-tumor immune responses and long-term immune-mediated survival. Phase 1 Toca 511 and Toca FC (extended-release 5-FC) clinical trials in patients with recurrent high-grade glioma show durable complete responses and promising survival data compared to historic controls...
March 30, 2018: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29312597/targeting-of-cd122-enhances-antitumor-immunity-by-altering-the-tumor-immune-environment
#4
Daniel O Villarreal, Michael J Allegrezza, Melissa A Smith, Diana Chin, Leopoldo L Luistro, Linda A Snyder
Mounting evidence demonstrates that CD8+CD122+ T cells have suppressive properties with the capacity to inhibit T cell responses. Therefore, these cells are rational targets for cancer immunotherapy. Here, we demonstrate that CD122 monoclonal antibody (mAb; aCD122) therapy significantly suppressed tumor growth and improved long-term survival in tumor-bearing mice. This therapeutic effect correlated with enhanced polyfunctional, cytolytic intratumoral CD8+ T cells and a decrease in granulocytic myeloid-derived suppressor cells (G-MDSCs)...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311384/myeloid-derived-suppressor-cells-immune-suppressive-cells-that-impair-antitumor-immunity-and-are-sculpted-by-their-environment
#5
REVIEW
Suzanne Ostrand-Rosenberg, Catherine Fenselau
Myeloid-derived suppressor cells (MDSC) are a diverse population of immature myeloid cells that have potent immune-suppressive activity. Studies in both mice and humans have demonstrated that MDSC accumulate in most individuals with cancer, where they promote tumor progression, inhibit antitumor immunity, and are an obstacle to many cancer immunotherapies. As a result, there has been intense interest in understanding the mechanisms and in situ conditions that regulate and sustain MDSC, and the mechanisms MDSC use to promote tumor progression...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29311360/myeloid-derived-suppressor-cells-mediate-inflammation-resolution-in-humans-and-mice-with-autoimmune-uveoretinitis
#6
Hyun Jeong Jeong, Hyun Ju Lee, Jung Hwa Ko, Bum-Joo Cho, Se Yeon Park, Jong Woo Park, Se Rang Choi, Jang Won Heo, Sun-Ok Yoon, Joo Youn Oh
Resolution of inflammation is an active process that leads to tissue homeostasis and involves multiple cellular and molecular mechanisms. Myeloid-derived suppressor cells (MDSCs) have recently emerged as important cellular components in the resolution of inflammation because of their activities to suppress T cell activation. In this article, we show that HLA-DR-CD11b+CD33+CD14+ human MDSCs and CD11b+Ly6G-Ly6C+ mouse MDSCs markedly increased in patients and mice during and before the resolution phase of autoimmune uveoretinitis...
January 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29306019/sirt1-and-hif1%C3%AE-signaling-in-metabolism-and-immune-responses
#7
Qing Yu, Lin Dong, Yan Li, Gaungwei Liu
SIRT1 and HIF1α are regarded as two key metabolic sensors in cellular metabolism pathways and play vital roles in influencing immune responses. SIRT1 and HIF1α regulate immune responses in metabolism-dependent and -independent ways. Here, we summarized the recent knowledge of SIRT1 and HIF1α signaling in metabolism and immune responses. HIF1α is a direct target of SIRT1. Sometimes, SIRT1 and HIF1α cooperate or act separately to mediate immune responses. In innate immune responses, SIRT1 can regulate the glycolytic activity of myeloid-derived suppressor cells (MDSCs) and influence MDSC functional differentiation...
January 3, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29303012/blockade-of-ccr5-mediated-myeloid-derived-suppressor-cell-accumulation-enhances-anti-pd1-efficacy-in-gastric-cancer
#8
Liu Yang, Bing Wang, Jian Qin, HengHua Zhou, Adhip P N Majumdar, Fei Peng
PURPOSE: Myeloid derived suppressor cells (MDSC) play an important role in tumor immune evasion and its level significantly increased in patients with gastric cancer. Studies confirmed the associations between MDSC and various cytokines in the peripheral blood. However, little is known about the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and CCR5 level in gastric cancer. MATERIALS AND METHODS: G-MDSC and M-MDSC from the peripheral blood and tumor parenchyma were analyzed by flow cytometry...
January 5, 2018: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/29301826/p53-reactive-t-cells-are-associated-with-clinical-benefit-in-patients-with-platinum-resistant-epithelial-ovarian-cancer-after-treatment-with-a-p53-vaccine-and-gemcitabine-chemotherapy
#9
Nicola R Hardwick, Paul Frankel, Christopher Ruel, Julie Kilpatrick, Weimin Tsai, Ferdynand Kos, Teodora I Kaltcheva, Lucille Leong, Robert Morgan, Vincent Chung, Raechelle Tinsley, Melissa Eng, Sharon P Wilczynski, Joshua D I Ellenhorn, Don J Diamond, Mihaela Cristea
PURPOSE: To conduct a Phase I trial of a Modified Vaccinia Ankara vaccine delivering wild type human p53 (p53MVA) in combination with gemcitabine chemotherapy in patients with platinum-resistant ovarian cancer. EXPERIMENTAL DESIGN: Patients received gemcitabine on days 1 and 8 and p53MVA vaccine on day 15, during the first 3 cycles of chemotherapy. Toxicity was classified using the NCI Common Toxicity Criteria and clinical response assessed by CT scan. Peripheral blood samples were collected for immunophenotyping and monitoring of anti-p53 immune responses...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29299660/reduction-of-myeloid-derived-suppressor-cells-reinforces-the-anti-solid-tumor-effect-of-recipient-leukocyte-infusion-in-murine-neuroblastoma-bearing-allogeneic-bone-marrow-chimeras
#10
Isabelle Dierckx de Casterlé, Sabine Fevery, Omer Rutgeerts, Fariba Poosti, Sofie Struyf, Caroline Lenaerts, Mark Waer, An D Billiau, Ben Sprangers
Allogeneic hematopoietic stem cell transplantation is an emerging treatment option for solid tumors because of its capacity to elicit immune graft-versus-tumor effects. However, these are often limited and associated with GvHD. Adoptive recipient leukocyte infusion (RLI) was shown to enhance anti-tumor responses of allogeneic bone marrow transplantation in murine neuroblastoma (Neuro2A)-bearing chimeras. In contrast to the clinically used donor leukocyte infusion, the RLI anti-tumor effect-elicited by host-versus-graft lymphohematopoietic reactivity-does not cause GvHD; however, the tumor growth-inhibitory effect is incomplete, because overall survival is not prolonged...
January 3, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29299180/regulation-of-pd-1-pd-l1-pathway-and-resistance-to-pd-1-pd-l1-blockade
#11
REVIEW
Jie Bai, Zhitao Gao, Xiang Li, Liang Dong, Weidong Han, Jing Nie
Immune checkpoint blockades, such as inhibitors against programmed death 1 (PD-1) and its ligand (PD-L1), have received extensive attention in the past decade because of their dramatic clinical outcomes in advanced malignancies. However, both primary and acquired resistance becomes one of the major obstacles, which greatly limits the long-lasting effects and wide application of PD-1/PD-L1 blockade therapy. PD-1/PD-L1 both regulates and is regulated by cellular signaling pathways and epigenetic modification, thus inhibiting the proliferation and effector function of T and B cells...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296839/pak2-regulates-myeloid-derived-suppressor-cell-development-in-mice
#12
Yi Zeng, Seongmin Hahn, Jessica Stokes, Emely A Hoffman, Monika Schmelz, Maria Proytcheva, Jonathan Chernoff, Emmanuel Katsanis
Myeloid-derived suppressor cells (MDSCs) are CD11b+Gr1+ cells that induce T-cell hyporesponsiveness, thus impairing antitumor immunity. We have previously reported that disruption of Pak2, a member of the p21-activated kinases (Paks), in hematopoietic stem/progenitor cells (HSPCs) induces myeloid lineage skewing and expansion of CD11bhighGr1high cells in mice. In this study, we confirmed that Pak2-KO CD11bhighGr1high cells suppressed T-cell proliferation, consistent with an MDSC phenotype. Loss of Pak2 function in HSPCs led to (1) increased hematopoietic progenitor cell sensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, (2) increased MDSC proliferation, (3) decreased MDSC sensitivity to both intrinsic and Fas-Fas ligand-mediated apoptosis, and (4) promotion of MDSCs by Pak2-deficient CD4+ T cells that produced more interferon γ, tumor necrosis factor α, and GM-CSF...
October 10, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296736/novel-gm-csf-signals-via-ifn-%C3%AE-r-irf-1-and-akt-mtor-license-monocytes-for-suppressor-function
#13
Eliana Ribechini, James A Hutchinson, Sabine Hergovits, Marion Heuer, Jörg Lucas, Ulrike Schleicher, Ana-Laura Jordán Garrote, Sarah J Potter, Paloma Riquelme, Heike Brackmann, Nora Müller, Hartmann Raifer, Ingolf Berberich, Magdalena Huber, Andreas Beilhack, Michael Lohoff, Christian Bogdan, Matthias Eyrich, Heike M Hermanns, Edward K Geissler, Manfred B Lutz
Granulocyte-macrophage colony-stimulating factor (GM-CSF) controls proliferation and survival of myeloid cells including monocytes. Here, we describe a time-dependent licensing process driven by GM-CSF in murine Ly6Chigh and human CD14+ monocytes that disables their inflammatory functions and promotes their conversion into suppressor cells. This 2-step licensing of monocytes requires activation of the AKT/mTOR/mTORC1 signaling cascade by GM-CSF followed by signaling through the interferon-γ receptor (IFN-γR)/interferon regulatory factor-1 (IRF-1) pathway...
June 13, 2017: Blood Advances
https://www.readbyqxmd.com/read/29291452/ifn-%C3%AE-decreased-the-suppressive-function-of-cd33-hla-drlow-myeloid-cells-through-down-regulation-of-pd-1-pd-l2-signaling-pathway
#14
Xiaoxia Zhan, Shengfeng Hu, Yongjian Wu, Miao Li, Ting Liu, Siqi Ming, Minhao Wu, Min Liu, Xi Huang
Myeloid-derived suppressor cells (MDSCs) have recently been described to inhibit protective T-cell responses in tuberculosis (TB). T cells play an important role in the immunity to Mycobacterium tuberculosis, and are the major producers of IFN-γ. However, the impact of IFN-γ on MDSCs during TB is still not completely understood. Our study demonstrated a significant correlation between MDSC levels and TB progression, suggesting that MDSCs may serve as a potential marker in diagnosis or treatment of TB. Culture with GM-csf and IL-6 promoted peripheral blood mononuclear cells (PBMCs) to differentiate into functional CD33+HLA-DRlow MDSC-like cells...
December 29, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29290791/a-novel-dna-aptamer-for-dual-targeting-of-polymorphonuclear-myeloid-derived-suppressor-cells-and-tumor-cells
#15
Haoran Liu, Junhua Mai, Jianliang Shen, Joy Wolfram, Zhaoqi Li, Guodong Zhang, Rong Xu, Yan Li, Chaofeng Mu, Youli Zu, Xin Li, Ganesh L Lokesh, Varatharasa Thiviyanathan, David E Volk, David G Gorenstein, Mauro Ferrari, Zhongbo Hu, Haifa Shen
Aptamers have the potential to be used as targeting ligands for cancer treatment as they form unique spatial structures. Methods: In this study, a DNA aptamer (T1) that accumulates in the tumor microenvironment was identified through in vivo selection and validation in breast cancer models. The use of T1 as a targeting ligand was evaluated by conjugating the aptamer to liposomal doxorubicin. Results: T1 exhibited a high affinity for both tumor cells and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs)...
2018: Theranostics
https://www.readbyqxmd.com/read/29284516/lack-of-socs3-increases-lps-induced-murine-acute-lung-injury-through-modulation-of-ly6c-macrophages
#16
Zhilong Jiang, Zhihong Chen, Liyang Li, Wenjun Zhou, Lei Zhu
BACKGROUND: SOCS3 (suppressor of cytokine signaling 3) is a negative regulator of JAK/STAT3 signaling pathway and participates in the regulation of lung inflammation in a mouse model with acute lung injury (ALI). However, it is not well understood how SOCS3 regulates lung inflammation in the ALI mouse model. METHOD: In the present study, we investigated the effects of SOCS3 on modulation of Ly6C(+) monocyte phenotypes in a mouse model with lipopolysaccharide (LPS)-induced ALI...
December 29, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29282300/scavenger-receptor-type-b1-and-lipoprotein-nanoparticle-inhibit-myeloid-derived-suppressor-cells
#17
Michael P Plebanek, Debayan Bhaumik, Paul J Bryce, C Shad Thaxton
Myeloid derived suppressor cells (MDSCs) are innate immune cells that potently inhibit T cells. In cancer, novel therapies aimed to activate T cells can be rendered ineffective due to the activity of MDSCs. Thus, targeted inhibition of MDSCs may greatly enhance T cell-mediated anti-tumor immunity, but targeted mechanisms remain obscure. Here we show, for the first time, that scavenger receptor type B-1 (SCARB1), a high-affinity receptor for spherical high-density lipoprotein (HDL), is expressed by MDSCs. Furthermore, we demonstrate that SCARB1 is specifically targeted by synthetic high-density lipoprotein-like nanoparticles (HDL NP), which reduces MDSC activity...
December 27, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29276217/roles-of-estrogens-on-myeloid-derived-suppressor-cells-in-cancer-and-autoimmune-diseases
#18
Jing Ren, Yayi Hou, Tingting Wang
No abstract text is available yet for this article.
December 25, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29275468/targeting-myeloid-derived-suppressor-cells-in-cancer
#19
Waseem Anani, Michael R Shurin
Myeloid derived suppressor cells (MDSC) represent only a minor fraction of circulating blood cells but play an important role in tumor formation and progression. They are a heterogeneous group of cells that influence the tumor microenvironment by depletion of amino acids, oxidative stress, decreased trafficking of antitumor effector cells, and increased regulatory T and regulatory dendritic cell responses. Investigational treatment strategies targeting MDSCs have attempted to inhibit MDSC development and expansion (stem cell factor blockade, modulate of cell signaling, and target MDSC migration and recruitment), inhibit MDSC function (nitric oxide inhibition and reactive oxygen and nitrogen species inhibition), differentiate MDSCs into more mature cells (Vitamins A and D, all-trans retinoic acid, interleukin-2, toll-like receptor 9 inhibitors, taxanes, beta-glucan particles, tumor-derived exosome inhibition, and very small size proteoliposomes), and destroy MDSCs (cytotoxic agents, ephrin A2 degradation, anti-interleukin 13, and histamine blockers)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29273486/merkel-cell-carcinomas-infiltrated-with-cd33-myeloid-cells-and-cd8-t-cells-are-associated-with-improved-outcome
#20
Thibault Kervarrec, Pauline Gaboriaud, Patricia Berthon, Julia Zaragoza, David Schrama, Roland Houben, Yannick Le Corre, Eva Hainaut-Wierzbicka, Francois Aubin, Guido Bens, Jorge Domenech, Serge Guyétant, Antoine Touzé, Mahtab Samimi
BACKGROUND: Merkel cell carcinoma (MCC) is a rare tumor of the skin with an aggressive behavior. Immunity is the main regulator of MCC development, and many interactions between lymphocytes and tumor cells have been proven. However, the impact of tumor-infiltrating myeloid cells (TIMs) needs better characterization. OBJECTIVE: To characterize TIMs in MCC and their association with other immune effectors and patient outcome. METHODS: MCC cases were reviewed from a historical/prospective cohort...
December 19, 2017: Journal of the American Academy of Dermatology
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